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41.
42.
Accumulation of filamentous tau in the cerebral cortex of human tau R406W transgenic mice 总被引:4,自引:0,他引:4 下载免费PDF全文
Ikeda M Shoji M Kawarai T Kawarabayashi T Matsubara E Murakami T Sasaki A Tomidokoro Y Ikarashi Y Kuribara H Ishiguro K Hasegawa M Yen SH Chishti MA Harigaya Y Abe K Okamoto K St George-Hyslop P Westaway D 《The American journal of pathology》2005,166(2):521-531
Missense mutations of the tau gene cause autosomal dominant frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), an illness characterized by progressive personality changes, dementia, and parkinsonism. There is prominent frontotemporal lobe atrophy of the brain accompanied by abundant tau accumulation with neurofibrillary tangles and neuronal cell loss. Using a hamster prion protein gene expression vector, we generated several independent lines of transgenic (Tg) mice expressing the longest form of the human four-repeat tau with the R406W mutation associated with FTDP-17. The TgTauR406W 21807 line showed tau accumulation beginning in the hippocampus and amygdala at 6 months of age, which subsequently spread to the cortices and subcortical areas. The accumulated tau was phosphorylated, ubiquitinated, conformationally changed, argyrophilic, and sarcosyl-insoluble. Activation of GSK-3beta and astrocytic induction of mouse tau were observed. Astrogliosis and microgliosis correlated with prominent tau accumulation. Electron microscopic examination revealed the presence of straight filaments. Behavioral tests showed motor disturbances and progressive acquired memory loss between 10 to 12 months of age. These findings suggested that TgTauR406W mice would be a useful model in the study of frontotemporal dementia and other tauopathies such as Alzheimer's disease (AD). 相似文献
43.
Yuji Mizukami Fujitsugu Matsubara Takuma Hashimoto Jiro Okumura Shigeru Matsukawa Kiyoo Tanishima 《Pathology international》1987,37(2):253-260
Amylase activity was measured in thyroid tissues of various thyroid diseases and was analysed electrophoretically. Normal thyroid tissues contained significant amounts of amylase (mean ± SD; 2.71 ± 1.15 lU/g of tissue), and their amylase isozyme was composed of a majority of salivary type isoamylase and other peculiar isoamylase. The statistical decrease of amylase activities in tissues of Graves' disease under hyperthyroldism, thyroid carcinoma, and most of thyroid adenomas were found (Graves' disease; 1.04 ± 0.41, carcinoma; 1.49 ± 1.10, adenoma (except five cases with high activity); 0.88 ± 0.49 IU/g tissue). Five of 18 cases of adenoma showed strikingly higher amylase activity in their tissues. Electrophoretical patterns of amylase isoenzymes in these five adenoma tissue were different from those of normal thyroid tissues. The cellular localization of amylase in the normal thyroid tissues and the adenoma tissues was also demonstrated immunohlstochemically. 相似文献
44.
Role of matrix metalloproteinases in failure to re-epithelialize after corneal injury. 总被引:4,自引:1,他引:4 下载免费PDF全文
M. E. Fini W. C. Parks W. B. Rinehart M. T. Girard M. Matsubara J. R. Cook J. A. West-Mays P. M. Sadow R. E. Burgeson J. J. Jeffrey M. B. Raizman R. R. Krueger J. D. Zieske 《The American journal of pathology》1996,149(4):1287-1302
Delayed re-epithelialization of the cornea after injury usually precedes stromal ulceration. Previous findings using a rat thermal injury model suggested that re-epithelialization is impeded by products of resident corneal cells, which destroy adhesive structures at the basement membrane zone. In this study, we provide additional evidence for this concept. Failure to re-epithelialize was found to correlate with an increase in the amounts of gelatinolytic matrix metalloproteinases present in the rat cornea. One of these gelatinases, gelatinase B, is synthesized by the resident corneal cells, and inhibitions of its synthesis correlated with inhibition of basement membrane dissolution. The matrix metalloproteinases collagenase and stromelysin are also synthesized by resident corneal cells in thermally injured corneas of rabbits, but the timing of bulk enzyme synthesis correlated more closely with deposition of repair tissue in the stroma than with failure to re-epithelialize. Nevertheless, in human corneas with repair defects, gelatinase B and collagenase are synthesized by cells in the basal layer of the epithelium directly adjacent to the basement membrane, suggesting that both could participate in dissolution of this structure. Importantly, treatment of thermally injured corneas with a synthetic inhibitor of matrix metalloproteinases significantly improved basement membrane integrity. These data support the concept that over-expression of matrix metalloproteinases by resident corneal cells impedes re-epithelialization after some types of corneal injury. 相似文献
45.
1. The equatorial X-ray diffraction pattern was recorded from a papillary muscle of a cross-circulated canine heart at different phases of the cardiac cycle. The intensity ratio of the 1, 0 and the 1, 1 reflexions (I1, o/I1,1) was 0-79 in the systolic phase and 1-19 in the diastolic phase. 2. Using the intensity ratio obtained, the approximate proportion of the myosin projections present in the vicinity of the thin filaments was calculated. This was 70-71% in the systolic phase and 51-52% in the diastolic phase of the total myosin projections. 3. The peak systolic tension was roughly proportional to the proportion of the projections present in the vicinity of the thin filaments during systole. 4. The projections which stayed in the vicinity of the thin filaments during diastole did not produce significant contractile force. 相似文献
46.
Y Mizukami K Saito A Nonomura T Michigishi T Hashimoto Y Nakanuma F Matsubara E Takasakura 《Acta pathologica japonica》1990,40(8):602-608
A 75-year-old woman with lung adenocarcinoma in whom autopsy revealed metastasis to microfollicular adenoma of the thyroid is described. A thyroid tumor specimen from this patient was initially interpreted as representing primary encapsulated follicular carcinoma of the thyroid associated with a component of poorly differentiated carcinoma of follicular cell origin. The widespread involvement of the lungs and other sites was also interpreted as metastases from the poorly differentiated carcinoma component within the encapsulated follicular carcinoma of the thyroid. Subsequent meticulous histologic examination revealed that the thyroid tumor was a microfollicular adenoma, and that the component of poorly differentiated carcinoma within it was the same as the lung carcinoma. Immunohistochemical investigation revealed that the poorly differentiated carcinoma cells within the thyroid tumor were stained positively with polyclonal and monoclonal antibodies against carcinoembryonic antigen (CEA) and negative for thyroglobulin and calcitonin. The carcinoma cells from the lungs and other sites also showed positive staining for CEA. These findings support the view that the component of poorly differentiated carcinoma was a metastatic lesion from the primary lung carcinoma to the microfollicular adenoma of the thyroid. The present study emphasizes that attention should be directed to thyroid metastasis, even if it is within a thyroid primary neoplasm. 相似文献
47.
The authors report a case of Wegener's granulomatosis with the unusual manifestation of diffuse pulmonary hemorrhage. A 58-year-old man complained of bloody sputum and fever. Chest X-ray films showed multiple nodular shadows in both lung fields. He was diagnosed as having Wegener's granulomatosis by transbronchial lung biopsy, which revealed necrotizing granulomatous inflammation with necrotizing vasculitis. Despite treatment with cyclophosphamide and prednisolone, his condition rapidly deteriorated. An extensive diffuse alveolar shadow appeared in both lung fields in chest X-ray films, anemia became worse, and he died of respiratory failure. Autopsy revealed diffuse alveolar hemorrhage with necrotizing capillaritis in addition to the typical pathological findings in Wegener's granulomatosis. The capillaritis was characterized by neutrophilic infiltration of alveolar septa, and fibrin thrombi in alveolar capillaries. Diffuse pulmonary hemorrhage is uncommon in Wegener's granulomatosis. However, once diffuse pulmonary hemorrhage occurs, the respiratory condition rapidly deteriorates and is life-threatening. Therefore, accurate diagnosis and appropriate treatment are required. 相似文献
48.
49.
Recent advances in human genome research have revealed that genetic polymorphisms, such as single nucleotide polymorphisms (SNPs), are closely associated with susceptibility to various common diseases and adverse drug reactions. Also, numerous mutations responsible for a number of genetic diseases have been identified. Clinical application of genetic information to individual health care requires simple and rapid identification of nucleotide changes in clinical settings. We have devised a novel low-tech method for the detection of a single nucleotide substitution using competitive allele-specific short oligonucleotide hybridization with immunochromatographic strip. The gene of interest is PCR-amplified, hybridized to an allele-specific short oligonucleotide probe in the presence of a competitive oligonucleotide, and subjected to chromatography using a DNA test strip at room temperature. The genotype is unambiguously determined by the presence or the absence of visible purple lines on a strip. Feasibility of the method was demonstrated by the detection of a prevalent disease-causing mutations in glycogen storage disease type Ia (G6PC), medium-chain acyl-CoA dehydrogenase deficiency (ACADM), non-ketotic hyperglycinemia (GLDC), and clinically important polymorphisms in the CYP2C19 gene and the aldehyde dehydrogenase 2 gene (ALDH2). The procedure does not demand either technical expertise or expensive instruments and is readily performed in local clinical laboratories. The result is obtained within 10 min after PCR. This rapid and simple method of SNP detection may be used for point-of-care genetic diagnosis with potentially diverse clinical applications. Hum Mutat 22:166-172, 2003. 相似文献
50.
Sakurai Y Shoji M Matsubara T Imazu H Hasegawa S Ochiai M Funabiki T Mizoguchi Y Kuroda M Kasahara M 《Pathology international》2000,50(8):655-659
Angiomyomatous hamartoma is a rare disease with a predisposition for the inguinal lymph nodes. A 51-year-old male patient visited a local hospital because of a right inguinal mass, measuring 3 x 4 cm in size, which was resected. The resected specimen showed irregularly distributed thick-walled vessels in the hilum, extending into the medulla and focally into the cortex of the node, eventually becoming more dispersed and associated with smooth muscle cells splaying into sclerotic stroma. These findings are compatible with an angiomyomatous hamartoma. Another tumor-like mass appeared shortly after the resection at the same location, but was not an angiomyomatous hamartoma, rather it was composed of edematous stromal tissue with proliferating smooth muscle cells. The stromal component included thick-walled blood vessels and lymphatics. Although it could not be determined whether these associated changes in the surrounding stroma are a cause or an effect of angiomyomatous hamartoma, they indicate the clinical difficulty in determining an appropriate area of resection and may provide clues to the pathogenesis of angiomyomatous hamartoma. 相似文献